Deamidation Assessment

bellasmithPublished: December 25, 2017
Published: December 25, 2017

The deamidation rate is influenced by three primary factors: pH, primary sequence and conformational effects. Antibody Exposure to alkaline pH results in an increased rate of succinimide formation due to greater deprotonation of the peptide bond nitrogen at higher pH values. Highest frequency for protein deamidation is the primary sequence with Asn-Gly, and intermediate frequency is Asn residues followed by a polar amino acid with a relative small side chain, like Ser, Thr and Asp. Asn residue followed by a hydrophobic amino acid with a bulky side chain has the lowest frequency for protein deamidation. The secondary and tertiary structure of protein can also alter the deamidation rate, as shown in two hotspots with the same primary sequence in the Fc regions of antibodies. The asparagine and its flanking residues must be solvent accessible and locate within a conformationally flexible region of the protein.

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